The elegant and scenic State Room was the venue for this year's memorable Boston Festival of Food and Wine, which took place on October 21st.  A record crowd displayed their passion and commitment for accelerating treatments and a cure for Rett Syndrome by raising an impressive $575,00, a 77% increase over last year's proceeds.  Congratulations are extended to the Festival Co-Chairs: RSRF Trustees, Michael Joyce, Chuck Curley and Christian McMahan and their wives Jane, Paula and Ariane. Their willingness to give of their time and effort and their ability to reach out to their family, friends and colleagues is deeply appreciated and will benefit everyone who loves a child with Rett Syndrome.

RSRF would like to thank Honorary Co-Chairs, Jack Connors of Hill Holiday and Bill Guerin of the Dallas Stars, for their role in making this event a huge success. We also would like to extend our appreciation to Greg Hill of WAAF-FM Radio and Lisa Hughes, News Anchor of CBS4 in Boston, for their role in the evenings program.  Lastly, we would like to acknowledge the generosity and support of our key sponsors:  Hill Holiday, Eastern Development Corporation and Suffolk Construction.

Our next issue of the RSRFlash, currently in the mail, will contain more information on this event. In the meantime, please visit our website to see photos of this  wonderful evening.

Bill Kolb, retiring Admissions Director for the University of Florida, wanted no part of retirement parties or other fanfare until his staff suggested an event in his honor to raise research funds to benefit Rett Syndrome (which afflicts his beloved 3 year-old granddaughter, Sydney.) Thankfully he agreed and RSRF is now pleased to have an additional $12,000 to spend on research! We extend our heartfelt thank yous to Bill and Sandy Kolb and to their daughter and son-in-law, Kristan and Scott Ellison. Bill, congratulations on your retirement and thank you for your continued commitment to finding a cure. To see photos of the event, please click here.

The Carmel Mountain Ranch Country Club in San Diego played host to the inaugural American Commercial Claims Administrators (ACCA) Golf Tournament. John Anderson, an employee of ACCA, and his wife Kami, have two daughters with Rett Syndrome. On October 8th, ACCA employees, along with their associates and vendors, hit the links to show their support for the Anderson's in the best way they knew how....by raising $31,000 for Rett research! Our sincere thanks to the Anderson family, ACCA and all of their wonderful friends. To see photos of the event, please click here.

RSRF's signature fundraising event, the Strollathon, debuted in Seattle on August 29th. We would like to thank Event Co-Chairs, Jeff and Laurie Huisingh, for a job well done! Special thanks also go out to sponsors, DHL and Ikea, as well as all of the team captains who led the fundraising effort. Our Seattle contingency is already working on next year's event which will take place at Bradley Lake Park in Puyallup, WA at a date to be determined. To see photos of the event, click here.

This study conducted in Belgium looked at 107 females with deletions in a certain section of the MECP2 gene. The paper shares some correlations they investigators drew between site of mutation and symptoms. Click here or on the title above to read the abstract and lay summary.

The authors of this paper investigated whether MECP2 mutations could be found in populations of patients who had non specific mental retardation but did not fit the criteria for Rett Syndrome. Click here or on the title above to read the abstract and lay summary.

This paper discusses a woman with atypical RTT symptoms and a mutation in MECP2 which to date has not been seen. Click here or on the title above to read the abstract and lay summary.

Mutant mice with an MECP2 mutation were studied so as to better understand their social interactions. Click here or on the title above to read the abstract and lay summary.

From a series of 107 females with Rett syndrome (RTT), we describe the long-term history of ten females with a deletion in the C-terminus of the MECP2 gene. We observed that their disorder profile is clinically recognizable with time and different from other atypical and milder RTT phenotypes. In females with hot spot deletions in the C-terminus, dystonia is present from childhood and results in a serious spine deformation in spite of preventive measures. Their adaptive behavior is surprisingly better preserved and in contrast with the typical decline in motor functioning. The delineaton of disorder profiles by long-term clinical observation can teach us about genotype/phenotype relationships and eventually about the effect of epigenetic phenomena on the final phenotype. (c) 2004 Wiley-Liss, Inc.

This study attempts to correlate symptoms (phenotype) with mutations (genotype) in an area of the MECP2 gene called the C-terminus which is located at the end of the gene. The authors studied 107 females with such mutations and concluded that overall these individuals were higher functioning then the typical person with RTT. They did present however with dystonia and severe scoliosis.

Mutations in the methyl-CpG-binding protein 2 (MECP2) gene are known to underlie Rett' syndrome, the most common cause of mental retardation (MR) in girls. Since the original report, phenotypes resulting from MECP2 mutations have been shown to extend, for example, to several Rett variants, autism, atypical Angelman syndrome, and nonspecific MR. It was earlier proposed that MECP2 mutations might account for approximately 2% of the male cases with nonspecific MR. Thereby, the frequency of MECP2 mutations in the mentally retarded population would be comparable to that of Fragile-X syndrome. The aim of this study was to analyze well-characterized cases with MR and to clarify the role of the MECP2 gene in the etiology of MR and atypical Angelman syndrome. The coding sequence of the MECP2 gene was analyzed in a sample of 118 patients (103 males, 15 females) by direct sequencing. Two coding sequence variants, 602C > T (A201V) and 1189G > A (E397K), were identified. In addition, we identified four variants in the intronic or 3'UTR regions. None of these variants is likely to be causal. We conclude that the evidence across all the mutation screening studies implies that MECP2 mutations do not represent a major cause of nonspecific MR. (c) 2004 Wiley-Liss, Inc.

MECP2 mutations have been identified in disorders that extend beyond Rett Syndrome. These investigators screened individuals with mental retardation for mutations in MECP2. They did not identify any disease causing mutations in the patients tested and therefore concluded that MECP2 mutations are unlikely to be the cause of non specific mental retardation.

We report a novel C-terminal MECP2 frameshift deletion (1135_1142delCCCGTG CC) in a 19-year-old woman with mental retardation and epilepsy. Preservation of language capabilities, purposeful hand use and sufficient locomotion implied an atypical variant of Rett syndrome (OMIM 312750). Occipito-frontal head circumference was large at birth (36 cm; SDS 1.7) and increased until adulthood (58.5 cm; SDS 2.3). CONCLUSION: Our observation indicates that head size and head growth are of limited reliability in the diagnosis of MECP2-associated phenotypes.

This study highlights the need for testing for MECP2 mutations even though the patient may not exhibit classic Rett symptoms criteria. A 19 year old woman who could speak, use her hands, walk and had normal head circumference growth but who had seizures and mental retardation was found to have an MECP2 mutation in the last part of the gene.

Rett syndrome (RTT) is an autistic spectrum disorder with a known genetic basis. RTT is caused by loss of function mutations in the X-linked gene MECP2 and is characterized by loss of acquired motor, social and language skills in females beginning at 6-18 months of age. MECP2 mutations also cause non-syndromic mental retardation in males and females, and abnormalities of MeCP2 expression in the brain have been found in autistic spectrum disorders. We studied home-cage behavior and social interactions in a mouse model of RTT (Mecp2(308/Y)) carrying a mutation similar to common RTT causing alleles. Young adult mutant mice showed abnormal home cage diurnal activity in the absence of motor skill deficits. Nesting, a phenotype related to social behavior, and social interactions were both impaired in these animals. Mecp2(308/Y) mice showed deficits in nest building and decreased nest use. Although there were no differences in aggression or exploration of novel inanimate stimuli, mutant mice took less initiative and were less decisive approaching unfamiliar males and spent less time in close vicinity to them in several social interaction paradigms. The abnormalities of diurnal activity and social behavior in Mecp2(308/Y) mice are reminiscent of the sleep-wake dysfunction and autistic features of RTT. These data suggest that MECP2 regulates the expression and/or function of genes involved in social behavior. The study of Mecp2(308/Y) mice will allow the identification of the molecular basis of social impairment in RTT and related autistic spectrum disorders.